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PULSATILE DRUG DELIVERY SYSTEM: A REVIEW


About Author: VIPUL P. PATEL1*, TUSHAR R. DESAI2, CHETAN R. MATHOLIYA, RAVI B. CHHAYANI
1. Assistant professor, Department of pharmaceutics, R. K. College of Pharmacy, Kasturbadham,Rajkot.
2. Principal, Department of pharmacology, R. K. College of Pharmacy, Kasturbadham,Rajkot.
3. Research Scholar, R. K. College of Pharmacy, Kasturbadham, Rajkot.                                                                                  

Reference ID: PHARMATUTOR-ART-1060

Abstract
Pulsatile Drug Delivery Systems are gaining a lot of interest as they deliver the drug at the right place at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release of the drugs is where a constant drug release is not desired. A pulse has to be designed in such a way that a complete and rapid drug release is achieved after the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. These systems are beneficial for the drugs having chronopharmacological behavior where night time dosing is required, such as anti-arhythmic and anti-asthmatic. Current review article discussed the reasons for development of pulsatile drug delivery system, types of the disease in which pulsatile release is required, classification, advantages, limitation, and future aspects of pulsatile drug delivery system.

Introduction
Over the last 30 years the pharmaceutical market has been demonstrated increasing preferably for controlled and targeted drug delivery system. Such systems have been focused on constant, variable; sustain drug release and/or targeting the therapeutic agent to a specific site/tissue/ organ. However, recently there are certain conditions for which such release pattern is not suitable. Such conditions that lead to the requirements of a time programmed therapeutic system, which capable of releasing drug after predetermined time delay and maintain constant drug levels throught the day. To introduce the concept of chronotherapeutics, it is important to define the following concepts.

Chronobiology: [4]
Chronobiology is the science concerned with the biological mechanism of the diseases according to a time structure.“Chrono” pertains to time and “biology” pertains to the study, or science, of life.

Chronopharmacology: [4]
Chronopharmacology is the science concerned with the variations in the pharmacological actions of various drugs over a period of time of the day.

Chronopharmacokinetics: [4,5]
Chronopharmacokinetics involves study of temporal changes in drug absorption, distribution, metabolism and excretion. Pharmacokinetic parameters, which are conventionally considered to be constant in time, are influenced by different physiological functions displaying circadian rhythm. Circadian changes in gastric acid secretion, gastrointestinal motility, gastrointestinal blood flow, drug protein binding, liver enzyme activity, renal blood flow and urinary pH can play role in time dependent variation of drug plasma concentrations.

Chronotherapy: [4]
Co-ordination of biological rhythms and medical treatment is called chronotherapy.

Chronotherapeutics: [4,6]
Chronotherapeutics is the discipline concerned with the delivery of drugs according to inherent activities of a disease over a certain period of time. it is becoming increasingly moreevident that the specific time that patients take their medication may be even more significant than was recognized in the past.

2. BIOLOGICAL RHYTHMS: [7]
1. Ultradian Rhythms:
Oscillations of shorter duration are termed Ultradian Rhythms (more than one cycle per 24 h). E.g.90 minutes sleep cycle.

2. Infradian Rhythms:
Oscillations that are longer than 24 hours are termed as Infradian Rhythms (less than one cycle per 24hours). E.g. Monthly Menstruation.

3. Circadian rhythms:
Circadian rhythms are self-sustaining, endogenous oscillations


Figure 1: Diseases displaying circadian rhythm [8]

that occur with a periodicity of about 24 Hours. Interestingly, the term circadian is derived from the Latin circa which means “about” and dies which can be defined as “a day”. Normally, circadian rhythms are synchronized according to internal biologic clocks related to the sleep-wake cycle. [7]

DISEASES AND CHRONOTHERAPEUTICS:
The potential benefits of chronotherapeutics have been demonstrated in the management of a number of diseases. In particular there is a great deal of interest in how chronotherapy can particularly benefit patients suffering from allergic rhinitis, rheumatoid arthritis and related disorders, asthma, cancer, cardiovascular diseases, and peptic ulcer disease. [6]

Table: 1 Disease Influenced by Chronotherapy [6]

Diseases

Influenced by Chronotherapy

 Cardiovascular

Hypertension,angina

, myocardial infarction

 Inflammatory

Rheumatoid arthritis, related disorders

 Neoplastic

Various forms of cancer

 Gastrointestinal

Peptic ulcer disease

 Respiratory

Allergic rhinitis, asthma

Cardiovascular Diseases: [6]
Cardiovascular diseases such as hypertension and angina, or chest pain, also follow a definite circadian rhythm.

Hypertension: [6]
Heart rate and blood pressure are increased in the early morning hours (morning or A.M. surge). The blood pressure declines form mid afternoon and is minimum at midnight. In most hypertensive patients, there is a rather marked rise in blood pressure upon awakening that is called the morning or “a.m.” Systolic blood pressure rises approximately 3mm Hg/hour for the first 4-6 hours post-awakening, while the rate of rise of diastolic blood pressure is approximately 2mm Hg/hour.


Fig.2: circadian variations in Blood Pressure [9]

Myocardial Infarction:
Onset of myocardial infarction has been shown to be more frequent in the morning with 34% events occurring between 6 A.M. and noon. Acute cardiac arrest and transient myocardial ischemia shows an increased frequency in morning. The causes for these findings have been suggested to be release of catecholamine, cortisol increase in the platelet aggregation and vascular tone. [4]
ACE inhibitors are more effective when administered during night. Atenolol, Nifedipine and amolodipine are more effective when administered at night.[4]


palak motan
Offline
Joined: 2010-06-06
re pulsatile delivery of antibiotic

sir, your article was very informative . sir. i am a M.pharm student and want todo project pulsatile delivery of antibiotic for travelers diarrohea since the dose of drug is 200mg 3 times a day. is my rationale of msking a pulsatile of antibiotic correct ? Please do reply

maheshrag (not verified)
Pulsatile drug delivery

Mr. Palak motan.......for the diseases which follow circadian rhythms, pulsatile drug delivery is useful.......so in the case of TD there is no need of PDDs. and

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